Articles in 2014

Traditionally, maintenance of gene silencing by the Polycomb group proteins has been thought to involve recruitment of Polycomb repressive complex (PRC) 1 by PRC2-mediated trimethylation of K27 on histone H3. Three recent studies challenge this model by demonstrating that monoubiquitination of histone H2A, which is catalyzed by PRC1 complexes, can recruit PRC2 and potentiate its catalytic activity.

ATP is continuously synthesized inside mitochondria and exported to the cytoplasm via transporter and channel proteins residing in the inner and outer mitochondrial membranes, respectively. In this issue of Nature Structural & Molecular Biology, a new crystal structure of the mitochondrial channel protein VDAC-1 provides the basis for a detailed simulation study that unravels the mechanism by which ATP diffuses across the outer mitochondrial membrane at a fast rate.

A randomized RNA library is used to determine the specificities of RNA recognition by PUF repeats. The code is then used to design a protein that targets endogenous human cyclin B1 mRNA and activates its translation.

Plk4 regulates centriole duplication. Two centrosomal scaffold proteins, Cep192 and Cep152, are shown to interact with Plk4 in a temporally and spatially regulated manner, and structural analyses reveal that these interactions are mutually exclusive.

A new system to monitor the effects of nucleosome depletion in Xenopus egg extracts reveals that nucleosomes are required for spindle assembly and for recruitment of nuclear pore complex (NPC) components to the nuclear envelope for NPC formation.

The X-ray crystal structure and biochemical analysis of a triple helix formed between the expression and nuclear retention element (ENE) and the 3′ poly(A) tail of the human long noncoding RNA MALAT-1 reveals the basis of its stability and how it confers resistance to degradation.

The first comprehensive analysis of the meiotic translational program of Schizosaccharomyces pombe by deep sequencing of ribosome-protected fragments identifies new translated sequences and highlights differences in the translational changes occurring during sexual differentiation of fission and budding yeasts.

Chang and colleagues report the involvement of a Dicer-microRNA-cMyc signaling axis in the transcriptional regulation of a large set of long noncoding RNAs (lncRNAs). These lncRNAs are specifically dependent on cMyc, as compared to divergently transcribed protein-coding genes.

Cancer-associated mutations in the pseudokinase domain (JH2) of JAK2 lead to constitutive activation of its tandem kinase domain (JH1). Molecular dynamics simulations, supported by mutational analysis, provide a model for JH2-JH1 interactions that explains many of the JAK2-activating disease mutations.

VDAC channels permeate metabolites from the mitochondrial intermembrane space to the cytosol. Markov state modeling, an approach used in protein-folding simulations, is now applied to examine ATP-permeation rates and pathways through mouse VDAC1.

A new study using fertilized mouse eggs shows that nuclear pore complex (NPC) formation is dependent on nucleosome assembly. Preventing de novo histone deposition on sperm chromatin results in formation of a paternal nuclear envelope lacking NPCs, thus indicating a role for nucleosomes beyond DNA packaging.

New high-resolution structures of microtubules reveal that GTP and taxol each stimulate microtubule assembly by inducing straight protofilaments and promoting extension of the interdimer spacing. However, these effects take place through different mechanisms: GTP directly extends loops around the active site, whereas taxol works like a remote lever.

X-ray structural analysis of spliceosomal U6 small nuclear RNA bound to Prp24 reveals a complex interlocked RNA–protein assembly and suggests models for key steps in spliceosome assembly and recycling.

Structural analyses reveal the asymmetric assembly of Neurospora crassa PAN2–PAN3 complex and, along with functional work on the proteins from different species, indicate an essential role for PAN3 in coordinating PAN2-mediated deadenylation with subsequent steps in mRNA decay.

Conti and colleagues present the crystal structure of the yeast deadenylase Pan2–Pan3 core complex, revealing a 1:2 stoichiometry and indicating how deadenylase and pseudokinase domains work together to promote RNA deadenylation.

PRC2 promotes methylation of H3K27, a modification that recruits PRC1, which in turn deposits H2A ubiquitin marks. Müller and colleagues use biochemistry approaches to show that H2Aub recruits Jarid–Aebp2–containing PRC2 to promote H3K27 trimethylation on H2Aub nucleosomes, thus forming a positive feedback loop to establish repressed chromatin domains.

Condensins organize chromosomes to allow proper segregation during mitosis or meiosis. Haering and colleagues show that the two HEAT-repeat subunits of the condensin complex, Ycg1 and Ycs4, bind DNA; this interaction stimulates ATPase activity of the SMC subunits and is required for condensin association with chromosomes.

During spliceosome assembly, U6 snRNA is recycled from U2 snRNA by the protein Prp24 and is paired with U4 snRNA to form a splicing-competent complex. A structure of yeast Prp24 bound to the conserved core of U6 RNA reveals a new arrangement of RNA-protein contacts that mediates these early events leading to pre-mRNA splicing.

Proudfoot, Gullerova and colleagues show that mammalian Dicer localizes to the nucleus, where its levels are tightly regulated. Dicer interacts with RNA polymerase II and seems to restrict double-stranded (ds) RNA formation from convergent transcription. Dicer knockdown leads to accumulation of dsRNA, triggering the interferon response pathway and cellular apoptosis.